Wnt/β-catenin signaling pathway in lung cancer stem cells is a potential target for the development of novel anticancer drugs.

PURPOSE

In the present study, we have analyzed the regulation of Wnt/β-catenin signaling in lung adenocarcinoma stem cells (CSCs), that are responsible for tumor recurrence.

METHODS

Lung cancer samples were studied for the presence of cancer stem like cells and analyzed by flow cytometry. Then, the sorted cells were analyzed for the stem cell surface markers and Wnt/β-catenin signaling pathways. Moreover, the sorted side population (SP) and non-SP cells were also subjected to drug resistance assay.

RESULTS

Western blot analysis showed that the protein level of β-catenin was highly upregulated in fluorescence activated cells (FACs) sorted SP cells which led to elevated expression of stem cell protein Oct-4 that is responsible for SP cells' self-renewal. RT-PCR revealed that the relative mRNA expression level of Wnt target gene cyclin D was significantly higher (p<0.01) in SP cells, enhancing thus the cell proliferation rate and clone formation efficiency. In addition, the matrigel invasion assay revealed that SP cells were highly invasive than non-SP cells.

CONCLUSION

In the present study we demonstrated that lung adenocarcinoma samples contain a small population of tumor-initiating SP cells which possess the characteristic features of CSCs. Wnt/β-catenin mediated increased expression of β-catenin, Oct-4 and cyclin D in SP cells but not in non-SP cells was also observed. FACs-purified SP cells are resistant to a number of chemotherapeutic drugs. Our data suggest that the use of novel anticancer drugs, targeting Wnt/β-catenin signaling pathways, may help eradicate the lung cancers stem cells.